There has been a growing interest in the application of microfluidic systems to a variety of technical areas, including such diverse fields as biochemical analysis, medical diagnostics, chemical synthesis, and environmental monitoring. Microfluidic systems provide certain advantages in acquiring chemical and biological information. For example, microfluidic systems permit complicated processes to be carried out using very small volumes of fluid, thus minimizing consumption of both samples and reagents. Chemical and biological reactions occur more rapidly when conducted in microfluidic volumes. Furthermore, microfluidic systems permit large numbers of complicated biochemical reactions and/or processes to be carried out in a small area (such as within a single integrated device) and facilitate the use of common control components. Examples of desirable applications for microfluidic technology include processes such as analytical chemistry; chemical and biological synthesis; DNA amplification; and screening of chemical and biological agents for activity.
Among the various branches of analytical chemistry, the field of chromatography stands to particularly benefit from microfluidic technology due to increased throughput afforded by performing multiple miniaturized-format analyses in parallel. Chromatography encompasses a number of applied methods that may be used for any of separation, identification, purification, and quantification of chemical or biochemical entities within various mixtures. In its most basic form, chromatography is a physical method of separation wherein the components to be separated are distributed between two phases, one of which is essentially stationary (the stationary phase) while the other (the mobile phase) moves in a definite direction. Separation results from differences in the distribution constants of the individual sample components between the two phases.
One subset of chromatography, liquid chromatography, utilizes a liquid mobile phase that typically includes one or more solvents. The stationary phase material typically includes packed particles having bound surface functional groups disposed within a tube commonly referred to as a “separation column.” A sample is carried by the mobile phase through the stationary phase material. As the sample solution flows with the mobile phase through the stationary phase, components of the sample solution will migrate according to interactions with the stationary phase and these components are retarded to varying degrees. The time a particular component spends in the stationary phase relative to the fraction of time it spends in the mobile phase will determine its velocity through the column. Following chromatographic separation in the column, the resulting eluate stream (i.e., mobile phase and sample components) contains a series of regions having elevated concentrations of individual species, which can be detected by various techniques to identify and/or quantify the species.
Although various motive forces such as pressure-driven flow or electrokinetic (voltage-driven) flow may be used in liquid chromatography, pressure-driven flow is desirable because it permits the use of a wide range of samples and solvents. Additionally, pressure-driven flow avoids problems inherently associated with high voltage systems—such as hydrolysis, which can lead to detrimental bubble formation. Within pressure-driven systems, higher pressures generally provide greater separation efficiencies, such that pressures of several hundred pounds per square inch (psi) or more are used in conventional liquid chromatography systems. So-called “high performance liquid chromatography” or “HPLC” systems that employ high operating pressures are widely used in various industrial and academic settings.
Because of the growing demand for liquid chromatographic analysis, it would be desirable to enable multiple pressure-driven chromatographic separations to be performed simultaneously, such as in parallel. Nonetheless, the ability to perform multiple parallel separations has been limited for a variety of reasons.
One obstacle to the development of parallel high-pressure fluidic systems has been providing fluidic interconnects capable of rapid operation while reliably sealing against leakage of high-pressure fluids. Conventional tube-based chromatography systems (e.g., employing columns contained by macro-scale or capillary tubing) typically utilize low-dead-volume threaded fittings. These fittings, however, are not well-suited for use in high-throughput (i.e., parallel) separation systems because: (1) they typically require individual assembly, which limits their ability to be rapidly operated; (2) they typically require circumferential access, thus limiting their ability to be arranged in close proximity to one another; and (3) they are difficult to automate due to the need to perform steps such as aligning mating components, rotating multiple screw fittings, and so on.
To promote rapid connection to microfluidic devices, a preferred interface type would operate by threadless engagement. One example of a threadless interface is provided in WIPO Internationial Publication Number WO 01/09598 to Holl et al., which discloses face sealing between a manifold having at least one protruding feature (e.g., a rigid tube) and a microfluidic device having an elastomeric outer layer. A bore defined in the protruding feature of the manifold is aligned with feature defined in the elastomeric outer layer of the microfluidic device such that when the protruding feature is pressed against the elastomeric outer layer, fluid can be communicated from the manifold into the microfluidic device or vice-versa. A common manifold may retain multiple tubes, and the sealing end face of each tube may have one or more ridges to provide improved sealing utility. One limitation of the Holl et al. interconnect is that it requires elastomeric materials. Elastomeric materials have limited utility in applications such as liquid chromatography, however, since they are generally incompatible with organic solvents typically used in chromatography and also may interact with samples in undesirable ways. For example, organic solvents commonly used in liquid chromatography can degrade elastomeric materials, thus causing degradation products to enter an eluate stream and potentially interfere with sample analysis. Additionally, molecules of a first sample may be adsorbed or otherwise temporarily bound to an elastomeric material during a first separation run, and such molecules may subsequently leach into an eluate stream containing a second sample during a second separation run, thus causing cross-contamination. Moreover, elastomeric materials are subject to mechanical wear, thus conferring limited service life to components constructed with them.
Additional types of threadless sealing interfaces for microfluidic devices are provided in U.S. Pat. No. 6,240,790 to Swedberg et al., which discloses various interconnect seals including the use of bosses and O-rings, direct/flat adhesive contact, sleeve fittings, and separate interconnects. These interconnect seals are disclosed for use with microanalysis devices preferably constructed by microfabricating a channel in the surface of a first substrate that mates with a second substrate in which a mirror-imaged channel has been fabricated to form a functional feature such as a separation channel. Certain of these sealing methods are ill suited for multi-use chromatography systems. For example, most O-rings are fabricated with soft materials that suffer from the same or similar drawbacks to the elastomeric materials discussed previously. O-rings are often ill-suited for repeated connection/disconnection cycles since they can come loose from their associated bosses or retention structures. In another example, the use of adhesives or material joining techniques utilizing direct bonding or ultrasonic welding usually provide permanent connections that may be incompatible with device designs that require temporary connections to enable periodic access to fluidic ports, such as for loading samples. If releasable (non-permanent) adhesives are used, the resulting interconnects typically pose chemical compatibility problems and may not seal against high operating pressures. Notably, Swedberg lacks details regarding specific channel configurations or other structures adapted to permit reliable fluidic interfaces at high operating pressures.
In light of the foregoing, it would be desirable to provide a re-useable fluidic interface to a microfluidic device capable of reliable, leak-free operation at high operating pressures without impairing operation of the microfluidic device. A desirable interface would also be threadless, permit rapid sealing and unsealing utility, and be characterized by minimal dead volume. Additionally, microfluidic devices to be used with the interface should preferably be easy to fabricate.
None of the figures are drawn to scale unless indicated otherwise. The size of one figure relative to another is not intended to be limiting, since certain figures and/or features may be expanded to promote clarity in the description.